Non-proteoglycan forms of biglycan increase with age in human articular cartilage

Abstract

Polyclonal anti-peptide antibodies were raised to the C-terminal regions of human biglycan and decorin. These antibodies were used in immunoblotting to study structural variations with age in the proteoglycan core proteins present in extracts of human articular cartilage and intervertebral disc. Three forms of the biglycan core protein were identified. The largest form was detected only after chondroitinase treatment and represents the proteoglycan form of the molecule from which the glycosaminoglycan chains have been removed. However, chondroitinase treatment did not alter the electrophoretic mobility of the two smaller proteins, which appear to represent non-proteoglycan forms of the molecule, resulting either from a failure to substitute the intact proteoglycan core protein with glycosaminoglycan chains during its synthesis or from proteolytic processing of the intact proteoglycan causing removal of the N-terminal region bearing the glycosaminoglycan chains. The non-proteoglycan forms constituted a minor proportion of biglycan in the newborn, but were the major components in the adult. A similar trend was seen in both articular cartilage and intervertebral disc. In comparison, decorin appears to exist predominantly as a proteoglycan at all ages, with two core protein sizes being present after chondroitinase treatment. Non-proteoglycan forms were detected in the adult, but they were always a minor constituent.

Glycosaminoglycan chains of biglycan promote bone morphogenetic protein-4-induced osteoblast differentiation

“…A related report showed that glycanated BGN is able to increase the phosphorylation of Smad1/5/8 (26). Markedly, it was reported that the levels of non-glycanated forms of BGN increase with age in human articular cartilage (27). A similar trend was observed in both articular cartilage and intervertebral discs.…”

Different Usage of the Glycosaminoglycan Attachment Sites of Biglycan

“…The N terminus of the propeptide was found to be generated by proteolysis at an unusual cleavage site be- tween Pro 18 and Phe 19 and not as often after a small amino acid (38). The predominant form of biglycan from the secretions of rat and bovine smooth muscle cells was generated by hydrolysis between Ala 16 and Leu 17 . However, an alternative rat propeptide sequence also began with Phe 19 , indicating that there might be either cell-and species-specific differences in the processing of the prepro peptide of biglycan or further degradation of the generated propeptide by aminopeptidases (39).…”

“…The propeptide whose function is not fully known is not necessarily removed prior to or after secretion (16). Additional proteolytic processing may take place after removal of the propeptide, accounting for nonglycanated forms of the molecule (17,18). The presence of only two glycosaminoglycan attachment sites that are located in close proximity made biglycan an ideal candidate to study glycosaminoglycan chain assembly in a still simple, yet somewhat more complex system than in the case of the monoglycanated small proteoglycan decorin, where glycosaminoglycan biosynthesis has been studied in great detail (2,7).…”

The Main Protein of the Aggregation Factor Responsible for Species-specific Cell Adhesion in the Marine Sponge Microciona prolifera Is Highly Polymorphic

“…Biglycan, a dermatan sulfate proteoglycan from articular cartilage, also exists as a nonproteoglycan form especially abundant in adults (75), suggesting different functional properties of biglycan during development, which would be linked to the extent of glycosylation. Differences in the carbohydrate structures of neural cell adhesion molecules modulate their binding properties during development (76,77).…”